Function of Coactivators in Progestin Action in Brain & Regulation of Behavior

University Of Massachusetts Amherst, Amherst MA

Investigators

Abstract

Steroid hormones act throughout the body to regulate development and reproduction by binding to receptors that activate specific genes in cells. The ovarian steroids, estradiol and progesterone, act in brain to mediate complex behaviors, such as female reproductive behavior in rodents. Thus, studying the function of estradiol and progesterone in rodent reproductive behavior provides an excellent model to investigate how hormones work in the brain. Understanding how these ovarian hormones act in brain is essential to understanding their role in various CNS functions. However, the cellular and molecular mechanisms by which steroid receptors activate genes in brain to control behavior are not well understood. Recently, a novel class of proteins, known as nuclear receptor coactivators, has been shown to dramatically enhance the ability of steroid receptors to activate genes. While research has led to a much greater understanding of the molecular mechanisms of these coactivators in steroid receptor action in the test tube, very little is known about how coactivators function in brain to regulate hormone-dependent gene expression and behavior. This grant will test the hypothesis that the two coactivators, Steroid Receptor Coactivator-1 (SRC-1) and CREB Binding Protein (CBP), are important in progesterone action in brain to regulate reproductive behavior. We predict that decreasing SRC-1 and CBP expression in specific brain regions will reduce progesterone-dependent reproductive behavior in rats. These studies will greatly enhance our understanding of how these novel coactivators work with steroid receptors to activate genes in brain.